Transient Anti-Drug Antibodies and Their Impact on Markers of Inflammation: Longitudinal Data From a 7-Year Study of Certolizumab Pegol in Crohnʼs Disease Patients
Bibliographic record
Abstract
Introduction: All biologics can induce anti-drug antibodies (ADA) that may influence the pharmacokinetic properties, efficacy and safety of the drug. Since ADA within and between individual patients (pts) have variable effects on drug concentrations, multiple tests may be needed to assess their clinical impact. The objective of this analysis was to describe and interpret the patterns of anti-certolizumab pegol antibodies (anti-CZP+), in CZP-treated patients, using plasma CZP concentrations and inflammation markers (C-reactive protein [CRP], fecal calprotectin [FCP]) from individual longitudinal data in the 7-year PRECiSE 3 study1 (P3, N=594). Methods: In PRECiSE 1 and 2 (P1/P2), FCP and CRP were assessed at Weeks 2, 4, 6, 8, 12, 16, 20, 24 and 26. In P3, FCP was assessed at Weeks 26, 54, 82, 106, 130, 158, 182, 210, 234, and 258; CRP was assessed at Week 2, every 4 weeks (Q4W) until Week 106, Q8W until Week 154, Week 158, Q8W until Week 258, Q12W until Week 354, and Week 364. CZP concentrations and ADA were measured at Weeks 2, 4, 6, 8, 12, 16, 20, 24 and 26 of P1/P2 and Week 2, Q4W until Week 106, Weeks 130, 158, 182, 210, 234, 258, 318, 364/or withdrawal visit and Week 364 or safety follow-up visit in P3. Anti-CZP+ was defined as >2.4 units/mL (by enzyme-linked immunoassay) on ≥1 occasion. Summary statistics were applied. Results: During P3, 22.5% of pts (n=134) had anti-CZP+ results on one or more occasions. Two critical patterns of anti-CZP+ were identified: 1) Transient anti-CZP+ had no effect or a transient effect on CZP plasma levels (Figure 1), and 2) persistent anti-CZP+ had a continuous impact on CZP plasma levels. Thirty percent (n=40) of anti-CZP+ pts were in the transient group and many continued with or completed P3. Significant differences between transient and persistent anti-CZP+ groups were observed in CZP plasma concentration, CRP, and FCP. (Figure 2) Pts with transient anti-CZP+ had comparable levels of CRP and FCP as pts who were anti-CZP negative.Figure 1Figure 2Conclusion: These data suggest that transient anti-CZP does not impact CZP levels or inflammation markers (CRP, FCP). Multiple assessments of anti-CZP may be necessary to inform therapeutic decisions. This observation is critical considering the importance of therapeutic drug monitoring in pts with Crohn's disease. Clinicaltrials.gov identifier: NCT00160524. Statement of funding: This study was sponsored by UCB Pharma.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.003 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".